CX-4945 is a potent, orally bioavailable inhibitor of casein kinase 2 (CK2; Ki = 0.38 nM) that competes with ATP by filling the small ATP binding site on the catalytic CK2α subunit, conferring selectivity. It inhibits proliferation in a panel of cancer cell lines that overexpress CK2 and prevents tumor growth of breast and pancreatic cancer cell xenografts in mice. CX-4945 blocks survival and induces apoptosis in cancer stem cells and is effective against glioblastomas and acute myeloid leukemia cells. CX-4945 also inhibits Cdc2-like kinases (Clk; IC50s = 82.3, 3.8, and 90 nM for Clk1, Clk2, and Clk3, respectively), interfering with alternative splicing.
